Molecular medicine holds much promise for advancing cancer diagnosis and treatment if biomarkers, molecular targets and drug effects on these targets can be accurately assessed in tumors. The amount and function of molecular drug targets within signal transduction pathways are often regulated by rapid enzymatic reactions in response to physiological stimuli. Biopsies play a central role in assessing biomarkers and molecular targets in solid tumors, but the traumatic process of cutting tissue samples by current biopsy devices perturb the tumor environment and thereby induce extraneous and confounding molecular responses to tissue trauma, bleeding and ischemia. Expeditious processing of the biopsy specimen using snap freezing or rapid fixation following tissue harvesting may be ineffective for preventing many rapid enzymatic modifications, because time frames of biopsy procedures and tissue handling before they are processed in the lab are longer than that of the enzymatic reactions. Moreover, artifacts from healthy tissue may reduce the accuracy of some types of biomarker analyses.
A method for tumor biopsy that preserves the molecular profile may facilitate pharmacodynamic assessment of targeted therapeutics and may also enable individualized molecular therapy of solid tumors based on accurate information about signal transduction pathways, molecular drug targets and biomarkers. This can maximize the efficacy of new directed chemotherapy agents by choosing the most appropriate patients for each type of therapy. As most of these therapies are associated with severe adverse effects and are highly expensive, individually directed therapy may eliminate suffering in patients that will not benefit from these therapies and can substantially reduce healthcare costs.
Many cancer patients do not benefit from the systemic treatments they receive. For example, an adjuvant chemotherapy regimen that is considered highly effective may often improve the disease-free or overall survival rate by only few percent. Also, chemotherapy for metastatic disease often provides sustained benefit for a small portion of the patients treated. Therefore, the medical therapies currently available to clinical practice expose far more patients than will benefit to the cost and toxicity of these agents. Although this over treatment is understandable in dealing with life-threatening diseases, the ability to better personalize treatment decisions could have important benefits for patients as well as reduce medical costs.
Biomarkers can be classified into two classes based on their mode of analysis: 1. Histology-based biomarkers adhere to specific structures in the tissue (e.g. cell membranes, chromosomes) and thus require intact tissue (e.g. immunohistochemical (IHC) and fluorescent in-situ hybridization (FISH)). In these tests tissue fixation can be done by chemicals (e.g. formalin-fixed paraffin-embedded, FFPE) or by freezing (e.g. frozen sections). These techniques can identify single or groups of cancerous cells in otherwise healthy tissue and may enable early detection of cancer. However, its processing is currently manual, time consuming and is difficult to standardize and quantify. 2. Content-based biomarkers are determined as the tissue concentration of specific molecules (e.g. proteins, RNA and DNA) that either have altered structure (e.g. DNA alterations) or abnormal levels in tumor cells. These biomarkers do not require the use of intact tissue, and typically involve tissue homogenate that is achieved by sample pulverization in the lab. Most of the studies on proteomic and genomic profiling of malignant tumors have been based on whole-tissue homogenate. However, their sensitivity may be reduced when non-homogenous tissue samples with a mixture of normal and cancerous cells are analyzed. It would be advantageous to have a biopsy system which enables preservation of biomarkers.
A cryogenic biopsy device is disclosed in U.S. Pat. No. 6,551,255. The device is configured for securing and coring of tumors within the body. An adhesion probe provides a coolant for adhering to the tumor and easing attachment of the tumor to the probe. However, the device disclosed therein does not disclose a system and method for providing frozen samples of tissue which may be analyzed histologically as well as via biomarker analysis while maintaining the molecular profile of the sample.
Thus, there is a need for a system and method for obtaining samples for content-based biomarker analysis wherein the molecular profiles of the samples can be stabilized during the procedure, and wherein sensitivity of biomarker analysis is enhanced by providing more homogenous tissue samples.